SBIR Phase I: Next-Generation Capillary Electrophoresis with Mass Spectrometry for Biopharmaceutical and Biomedical Applications

SBIR 第一阶段：用于生物制药和生物医学应用的下一代毛细管电泳和质谱分析

• 批准号: 1842394
• 负责人: Oluwatosin Dada
• 金额: $ 22.5万
• 依托单位: GMJ TECHNOLOGIES, LLC
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-02-01 至 2020-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1842394&HistoricalAwards=false
• 关键词: SBIR; Phase; Next; Generation; Capillary

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) project will be the development of a robust capillary electrophoresis instrument with mass spectrometry detection for biomedical research, biopharmaceutical development, clinical diagnostics, and system biology. Capillary electrophoresis (CE) is a powerful liquid separation technology with remarkable potentials for bioanalysis. It was the workhorse tool for the completion of human genome project that, in part, led to the DNA sequencing market. A CE system with both optical and mass spectrometry detection will enable a deeper understanding of molecular dynamics governing biochemical processes, such as protein expression, deregulation, and interaction with other biochemical species, which could lead to breakthroughs in drug development, early diagnosis, and treatments for deadly human diseases such as cancer, diabetics, and neurodegenerative disorders. The proposed technology will offer benefits to biopharmaceutical drug development companies by increasing the efficiency of product characterization for quality improvement. It also will allow efficient routine proteomics analysis and other bioanalytical applications.The intellectual merit of this SBIR Phase I project is to develop a next-generation capillary electrophoresis with electrospray ionization mass spectrometry (CE-ESI-MS) for protein characterization. CE-ESI-MS allows high efficiency separation and characterization of several biochemical species including proteins. However, leveraging the intrinsic advantages of CE-ESI-MS has been difficult due to lack of robust, easy-to-use instrumentation, which has made adoption for routine applications uncommon. This research will develop and evaluate a novel CE-ESI-MS instrument for protein characterization. The proposed instrument will employ original innovations to overcome the limitations of the incumbent technologies and exceed their capabilities. A novel fluidic nanoport for sample and buffer manipulation will be developed to allow analysis from 1 microL or less sample volume. The nanoport will employ a fully automated design with less operator intervention. This will be useful for sample-limited applications such as in clinical analysis. In addition, the instrument will utilize a hybrid electrospray ionization interface for simultaneous optical and MS detection, which no existing technology offers. Combining CE's ultrahigh efficiency with robust quantitative characteristics of optical detection and the molecular identification of mass spectrometry will be a powerful tool for bioanalysis. This combination will represent a significant advancement over the state-of-the-art and enhance the means of interrogating proteins and their biochemical functions in biological samples. The proposed innovations will significantly enhance the robustness and capabilities of CE-ESI-MS for fast, efficient, and deep bioanalysis.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

这个小企业创新研究（SBIR）项目的更广泛的影响/商业潜力将是开发一种强大的毛细管电泳仪器，用于生物医学研究，生物制药开发，临床诊断和系统生物学。 毛细管电泳（CE）是一种高效的液体分离技术，在生物分析中具有巨大的应用潜力。它是完成人类基因组计划的主力工具，在一定程度上导致了DNA测序市场。 具有光学和质谱检测的CE系统将能够更深入地了解控制生化过程的分子动力学，例如蛋白质表达，失调以及与其他生化物种的相互作用，这可能导致药物开发，早期诊断和治疗致命的人类疾病，如癌症，糖尿病和神经退行性疾病的突破。拟议的技术将通过提高产品表征的效率来提高质量，从而为生物制药药物开发公司带来好处。SBIR第一阶段项目的智力价值是开发下一代毛细管电泳-电喷雾电离质谱（CE-ESI-MS）用于蛋白质表征。CE-ESI-MS可以高效分离和表征包括蛋白质在内的多种生物化学物质。然而，由于缺乏强大的，易于使用的仪器，利用CE-ESI-MS的固有优势一直很困难，这使得常规应用的采用变得不常见。本研究将开发和评估一种新的CE-ESI-MS蛋白质表征仪器。拟议的工具将采用原始创新，以克服现有技术的局限性，并超越其能力。将开发用于样品和缓冲液操作的新型流体纳米孔，以允许从1微升或更少的样品体积进行分析。纳米端口将采用全自动设计，操作员干预较少。这将是有用的样品有限的应用，如在临床分析。此外，该仪器将利用混合电喷雾电离接口，同时进行光学和MS检测，这是现有技术所不能提供的。将毛细管电泳的快速检测效率与光学检测的强有力的定量特征和质谱的分子鉴定相结合，将成为生物分析的有力工具。这种组合将代表对现有技术的重大进步，并增强询问生物样品中蛋白质及其生化功能的手段。拟议的创新将显著增强CE-ESI-MS的稳健性和快速、高效和深入生物分析的能力。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Laser-induced fluorescence detector with a fiber-coupled micro GRIN lens for capillary electrophoresis

• DOI: 10.1364/ao.391661
• 发表时间: 2020-06-01
• 期刊: APPLIED OPTICS
• 影响因子: 1.9
• 作者: Dada, Oluwatosin O.